Vitamin A deficiency is chronic in many areas of the world. The first lines of defense against respiratory disease are the cells and immunoglobulins of the nasal mucous membranes. Vitamin A deficiency affects the production of mucous, the production of lymphoid cells, and the regeneration of mucous membranes following desquamation. Our study model was designed to investigate the mechanisms by which vitamin A deficiency cripples the normal nasal defenses. The model animal is the chicken; among small laboratory animals, its intranasal architecture and cell systems most closely resemble the human. Three related approaches are followed: (1) Organ and tissue cultures of respiratory mucous membranes from chicks deprived of vitamin A are maintained in media containing serum from these same chicks; these show the well-recognized sequence of changes characteristic of A-deficiency much earlier than in vivo systems, and show poor outgrowth of ciliated cells. (2) Chickens raised on an A-deficient diet are subsequently infected intranasally with Newcastle disease virus; bursal and thymic lesions are rapidly exacerbated by virus, thymic cortical lymphocytes are autophagocytosed, nasal lesions regenerate abnormally. (3) Baseline electron miroscope studies of the normal mucociliary interface show that both intra- and extracellular mucus is heterogeneous and that the shaggy underneath surface of the secreted blanket is in contact with cilia tips during the propulsive stroke.